Document Type
Article
Language
eng
Format of Original
11 p.
Publication Date
3-2016
Publisher
Elsevier
Source Publication
Free Radical Biology and Medicine
Source ISSN
0891-5849
Abstract
A novel rat model for a well-characterized human mitochondrial disease, mitochondrial DNA depletion syndrome with associated deoxyguanosine kinase (DGUOK) deficiency, is described. The rat model recapitulates the pathologic and biochemical signatures of the human disease. The application of electron paramagnetic (spin) resonance (EPR) spectroscopy to the identification and characterization of respiratory chain abnormalities in the mitochondria from freshly frozen tissue of the mitochondrial disease model rat is introduced. EPR is shown to be a sensitive technique for detecting mitochondrial functional abnormalities in situ and, here, is particularly useful in characterizing the redox state changes and oxidative stress that can result from depressed expression and/or diminished specific activity of the distinct respiratory chain complexes. As EPR requires no sample preparation or non-physiological reagents, it provides information on the status of the mitochondrion as it was in the functioning state. On its own, this information is of use in identifying respiratory chain dysfunction; in conjunction with other techniques, the information from EPR shows how the respiratory chain is affected at the molecular level by the dysfunction. It is proposed that EPR has a role in mechanistic pathophysiological studies of mitochondrial disease and could be used to study the impact of new treatment modalities or as an additional diagnostic tool.
Recommended Citation
Bennett, Brian; Helbling, Daniel; Meng, Hui; Jarzembowski, Jason; Geurts, Aron M.; Friederich, Marisa W.; Van Hove, Johan L.K.; Lawlor, Michael W.; and Dimmock, David P., "Potentially Diagnostic Electron Paramagnetic Resonance Spectra Elucidate the Underlying Mechanism of Mitochondrial Dysfunction in the Deoxyguanosine Kinase Deficient Rat Model of a Genetic Mitochondrial DNA Depletion Syndrome" (2016). Physics Faculty Research and Publications. 120.
https://epublications.marquette.edu/physics_fac/120
Comments
Accepted version. Free Radical Biology and Medicine, Vol. 92 (March 2016): 141-151. DOI. © 2016 Elsevier Inc. Used with permission.
Dr. Brian Bennett was affiliated with the National Biomedical EPR Center, Department of Biophysics, Medical College of Wisconsin at the time of publication.